Temporomandibular joint disorders (TMDs) are an important national health problem affecting more than 10 million people in the United States. Although the exact cause of TMDs is unclear, the temporomandibular joint (TMJ) disc pathophysiology (i.e., disc derangement and degeneration) is central to many TMDs. Poor nutritional supply to the TMJ disc as well as failure of mechanical function caused by pathological mechanical loading are believed to be the major biomechanical mechanisms for TMJ disc derangement and degeneration. The long-term goal of this project is to elucidate the roles of fluid and solute transport in TMJ disc mechanical function and cell nutrition for delineating the biomechanical etiology of TMDs in order to develop new strategies for restoring tissue function. Due to the unique composition and structure of the materials in the TMJ disc, as well as the complexity of the mechano-electrochemical coupling phenomena, there is a lack of knowledge about transport properties of the TMJ disc and appropriate theoretical models for investigating fluid and nutrient transport in the TMJ disc systematically. Therefore, the Specific Aims of this proposal are to: 1) evaluate the effect of mechanical strain on the transport properties of the TMJ disc and develop constitutive relationships between transport properties and tissue biochemical composition;2) examine the effect of changes in fluid transport properties on the tissue mechanical function and establish fluid flow dependent mechanisms for disc loading support and lubrication. To accomplish Specific Aim 1, we will: a) determine hydraulic permeability, fixed charge density, and electrical conductivity of porcine TMJ disc under various mechanical strains;b) obtain ion diffusivities from electrical conductivity data and develop new constitutive relationships between transport properties (hydraulic permeability and solute diffusivity) and tissue hydration to establish strain-dependent transport properties. To accomplish Specific Aim 2, we will determine time-dependent interstitial fluid pressure, fluid load support, and friction coefficient of porcine TMJ disc under sustained mechanical loading, and correlate fluid load support and friction coefficient to interstitial fluid pressure. These studies will provide new insights into a bio-transport related mechanism for disc degeneration and provide baseline material properties for developing biomechanical model to fully understand TMJ disc function and pathology. This work will support future R01 applications in which we will propose to develop a new multiphasic mechano-electrochemical finite element model of the TMJ disc which will provide details of mechanical stress, strain, fluid pressure, nutrient concentrations, electrical potential, fluid flow, and transport of nutrients within the TMJ disc under physiological or pathological loading conditions. We will also propose to study the biological response of disc cells to these physicochemical signals for fully elucidating biomechanical etiology of TMJ disc degeneration. Public Health Relevance: The goal of this project is to elucidate the roles of fluid and solute transport in tissue mechanical function and cell nutrition of the temporomandibular joint (TMJ) disc in order to delineate the biomechanical etiology of TMJ disorders and to develop novel, less-invasive diagnostic tools and new strategies for restoring tissue function. Therefore, this project will establish baseline measurements for the pig and generate biomechanical models that can be tested. In future studies we will use the pig to test these models further, compare different regenerative regimens, as well as design and evaluate human replacement TMJ tissues.